A heterocyclic compound has a basic framework of a natural product, and in particular, a piperidine-based derivative and a tetrahydroquinoline-based derivative, having a substituent, are widely used as an important intermediate and an important synthetic unit in pharmaceutical industries such as alkaloids, pharmaceutical products and agrichemical products, and material industries, such that methods of preparing these derivatives have been variously researched.
As a method of synthesizing the piperidine-based derivative and the tetrahydroquinoline-based derivative, having the substituent, a reduction method of N-heteroaromatic cyclic compounds such as a pyridine-based derivative and a quinoline-based derivative has been known.
In the reduction of the N-heteroaromatic cyclic compound has a significantly high reaction barrier, unlike a reduction of a hydrocarbon-aromatic cyclic compound, there is deactivation or poisoning pathway with respect to a reducing agent or a catalyst due to high basicity of a sp3-nitrogen atom newly produced from a reaction product, and there are no chemical- and regio-selectivity, which is partially reduced.
One of the known reduction methods of the N-heteroaromatic cyclic compound is to use a stoichiometric metal hydride including NaBH4, LiAlH4 or reactive metals (for example: Na), which may have problems such as limited ranges of starting materials, a large amount of waste, and the like, in addition to the above-described problems.
In addition, a reduction reaction of the N-heteroaromatic cyclic compound using hydrogen gas (H2) under a metal-mediated condition or a metal-free condition is also performed under high pressure (H2) and increased temperature, which causes formation of excessively reduced products, such that there is a limitation in introducing functional groups.
Further, in the case of a reduction method of the N-heteroaromatic cyclic compound using hydrosilane under a metal-mediated condition, partially reduced products may be formed, which do not have regioselectivity.
That is, as described above, the existing reduction of the N-heteroaromatic cyclic compound requires severe reaction conditions or shows low regioselectivity through multi-steps, and sometimes requires the use of high-priced metal catalyst.
Therefore, there is a need for a simpler and economical process under a mild condition, completely excluding the severe reaction conditions, the multi-step synthesis, and the use of high-priced metal catalyst required in the existing known methods.